Capacities of mouse embryo cells for induction of unscheduled DNA synthesis by 4-nitroquinolone 1-oxide in primary culture systems.
Because of 4-nitroquinoline 1-oxide (4-NQO) selectively induces lung tumors in offspring of ICR/Jcl inbred mice, unscheduled DNA synthesis (UDS) induced by 4-NQO was investigated with use of confluent primary cultures of cells from six different organs of ICR/Jcl mouse embryos. The UDS level of lung-derived cells (lung cells), as measured with hydroxyurea-resistant incorporation of [3H]thymidine into cellular DNA in the presence of 4-NQO, was at least threefold lower than levels in cells from skin, intestine, kidney, liver, and brain, when compared at equitoxic doses of 4-NQO of equimolar binding of 4-NQO to DNA Autoradiographic studies also revealed that the percentage of UDS-positive nuclei in lung cells was about one-fifth of other cell types. Cytotoxic examinations showed that the lung cells were the most sensitive to the lethal action of 4-NQO. These results suggest that the capacity of cells from the target organ to repair 4-NQO damage is intrinsically much lower than the capacity of cells from nontarget organs.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009600:Nitroquinolines / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D009600:Nitroquinolines; D015112:4-Nitroquinoline-1-oxide; D013936:Thymidine